Foresight Update 36

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Nadrian Seeman's NYU Team Creates A DNA-based Nanomechanical Device

Dr. Nadrian C. Seeman and his co-workers at New York University announced in January a major advance along one potential path toward molecular nanotechnology that involves making devices from branched DNA molecules. Seeman received Foresight's 1995 Feynman Prize in Nanotechnology for earlier work leading to this goal.

Their work was reported in the 14 January 1999 issue of Nature ["A nanomechanical device based on the B - Z transition of DNA," by Chengde Mao, Weiqiong Sun, Zhiyong Shen & Nadrian C. Seeman, Nature, 397: 144-146]. A brief description of the device, its operation, and graphics, can be found on the web site maintained by Dr. Seeman's lab at http://seemanlab4.chem.nyu.edu/device.html

The researchers say that the construction of this device is a first step towards the development of nano-robots that might some day construct individual molecules in molecular-scale factories. Describing the results, Dr. Seeman said, "Using synthetic DNA as a building material, we have constructed a controllable molecular mechanical system. In the short-run, this is an exciting technical achievement. In the long-term, the work will have implications for the development of nano-scale robots and for molecular manufacturing."

Constructed from synthetic DNA molecules, the device has two rigid arms that can be rotated between fixed positions (see Figure). The device consists of two rigid DNA 'double-crossover' molecules connected by a long DNA helix of 4.5 double-helical turns.

By introducing a positively charged cobalt compound into the solution surrounding the DNA molecules, the bridge region is converted from the right-handed B-DNA structure (top) to the left-handed Z-DNA structure (bottom). The arms of the molecule rotate from their initial position into the Z structure. (Note that the X and Y helices are now on opposite sides of the bridge.) Their relative repositioning was detected through fluorescent resonance energy transfer spectroscopy, which measures the relative proximity of two dye molecules attached to the "arms" of the DNA molecule, indicated by the X and Y dots in the figures. In the B-DNA structure, the two dyes are 20 angstroms closer to each other than they are in Z-DNA form.

The specificity of nucleotide base-pairing allows strands of DNA to be 'programmed' to self assemble in well-defined ways. Seeman's team took advantage of this fact to assemble two synthetic "double-crossover" (DX) DNA molecules. They are joined by a bridge segment (indicated in the diagram) containing the classical right-handed DNA structure called B-DNA. The bridge segment is a specific sequence of DNA base pairs that can be switched from the normal B-form (right-handed) DNA to Z-form (left-handed) DNA when the solution is changed by increasing salt concentration or adding certain small effector molecules (cobalt hexamine in these experiments).

The ends of all helices are closed by short sections of single strand DNA so that the entire structure is made from three cyclic strands of DNA that are multiply concatenated to link the rigid end structures with the central helix containing the switchable bridge section.

To measure the effects of the B <> Z DNA transition, two fluorescent dye molecules (fluorescein and Cy3) were attached to hairpin loops of DNA near the center of the construction (labeled "X" and "Y" in the illustration). The distance between these molecules was expected from molecular modeling calculations to increase from 5.1 nm to 7.0 nm as the transition from B to Z DNA caused the central helix to unwind by 3.5 helical turns.

The actual increase in separation was measured by fluorescence resonance energy transfer, which is proportional to the inverse sixth power of the distance between the dye molecules. The experimental results indicate an increase in separation between the dye molecules from 7.0 nm to 8.9 nm when the cobalt hexamine is added. No change was seen in a control construction in which the central helix was altered to a sequence that would not change to Z-DNA.

The DNA nanomechanical device is the culmination of a series of experiments in Dr. Seeman's lab involving synthetic DNA structures.

Dr. Seeman was awarded the 1995 Feynman Prize in Nanotechnology (see Foresight Update 23, available on the web at http://www.foresight.org/Updates/Update23/Update23.1.html#anchor415574) in recognition of his pioneering work to synthesize complex three-dimensional structures with DNA molecules. The Feynman Prize is given biennially by Foresight Institute in recognition of scientific work that most advances the development of molecular nanotechnology.

Creation of the B <> Z DNA nanomanipulator concept was blocked until now by the excessive floppiness of the DNA junction molecules that were available prior to using double crossover molecules of DNA. As Dr. Seeman told Foresight, "The stiff DX units used both in the 2D crystal and in the device were reported to be stiff in 1996 [X. Li, X. Yang, J. Qi, and N.C. Seeman, "Antiparallel DNA Double Crossover Molecules as Components for Nanoconstruction," Journal of the American Chemical Society, 118, 6131-6140 (1996)]. It just took that long to implement the two projects. In fact, we knew that they were stiff as early as late 1994."

Dr. Seeman and his colleagues conclude their paper on the nanomechanical device:

"It should be possible to incorporate this mechanical control in any figure or array produced by DNA nanotechnology, so long as a free swivel containing proto- Z DNA can be included in the design. In addition, it should be possible to change the relative positions of proteins or other large molecules connected to DX [DNA double crossover] units, in the same way that the relative positions of fluorescent dyes have been changed here. This capability should enable the study of proximity effects in chemical and biological systems. It is difficult to predict whether this system could also be used to power a nanoscale motor; we have shown that the B <> Z transition can provide two equilibrium structures in different positions, but the ability to transmit force depends on the structural and dynamic features of the transition itself."

At this early stage of development, it is not known whether the precision with which these DNA nanomanipulators could be programmed to deliver a precise force at a precise position would be adequate for mechanosynthesis. Dr. Seeman told Foresight: "The size of the DNA molecules is large, but we do not yet know the dispersion of 'before' and 'after' distances of molecules pendant from the DNA. Thus, it is premature to estimate the ability [or inability] of this system to position molecules precisely." However, designs that use such mechanisms to assemble molecular building blocks might be very interesting.

Budget request from the President could come as early as next year

The possibility of a high-level national initiative in nano-scale science and nanotechnology was the focus of a three-day workshop, "Vision for Nanotechnology R&D in the Next Decade," held at the National Science Foundation (NSF) in Arlington, VA, on 27-29 January. The workshop was organized by the Interagency Working Group on Nano Science, Engineering & Technology (IWGN).

According to a report in The Federal Technology Report (11 Feb 1999), nearly 100 specialists from federal and national laboratories, universities and industry participated. Presentations were made by staff from a variety of federal funding agencies with relevance to nanotechnology, including the NSF, NASA, the National Institutes of Health (NIH) and the Depts. of Energy and Defense.

The NSF also held a public forum, "From Scientific Discovery to the Nanotechnology of Tomorrow," during the Sixth Foresight Conference last November (http://www.foresight.org/Conferences/MNT6/NSF.html). Reports on the forum appeared in the Update 35, and are available on the Foresight web site at http://www.foresight.org/Updates/Update35/Update35.2.html#NSFforum

According to the announcement published in The Federal Register last December, the stated goal of the January Arlington workshop was "To identify goals, opportunities and policies pertaining to support for R&D in nanotechnology and related fields at NSF and other U.S. government agencies." The agenda included discussion on issues, opportunities, and future directions for nanotechnology research and development.

Following the workshop, senior federal officials are considering organizing a national nanotechnology initiative that could be included next year in President Clinton's federal budget request for Fiscal Year 2001. Vice President Al Gore announced a similar initiative, the Information Technology Initiative for the 21st Century (IT2), last January, which will be included in the President's FY-2000 budget request.

Thomas Kalil, a senior director for economic policy at the White House National Economic Council, issued a call for such an R&D effort organized at the national level during the workshop. Such an initiative, said Kalil, would have five major components: Increased investment; high-level attention; multi-agency cooperation; a rationale for the topic being a high priority; and a strategy that articulated "some relationship between the means and the ends."

The range of potential applications for nanotech devices or systems, and the benefits they may offer is impressive in its breadth, Kalil told workshop attendees. It offers "potential for a huge, pervasive impact on our economy [and] quality of life and requires and will enable advances in many disciplines," he said.

Kalil pointed to the increasing activity and growing interest among researchers and a "flurry of recent results" in the burgeoning field of nanotechnology. He also recalled the 1992 Senate hearings held by then-Senator Al Gore, which were the first congressional hearings on nanotechnology. K. Eric Drexler, a research fellow at the Institute for Molecular Manufacturing and a Foresight director, testified at those hearings. Dr. Drexler's written testimony appeared in Update 14, and is available on the Foresight web site at http://www.foresight.org/Updates/Update14/Update14.1.html; and a transcript of his oral testimony appeared in Update 15, available at http://www.foresight.org/Updates/Update15/Update15.1.html

Kalil also reminded workshop attendees of an April 1998 forecast by Neal Lane, the President's Science and Technology Advisor, that nanoscale science and engineering was the "most likely area of science and engineering to produce the breakthroughs of tomorrow." (See Update 33, on the web at http://www.foresight.org/Updates/Update33/Update33.1.html).

A report based on presentations and other contributions from workshop attendees during breakout sessions is in preparation. Their recommendations on the size, scope, directions and components for a National Nanotechnology Initiative will likely be delivered to OSTP and NSTC officials in the coming months. The next step would be a formal proposal drafted by NSTC, to be considered for inclusion in the administration's science and technology budget planning process for FY 2001.

The possibility was also raised that the initiative could be considered as an additional program during FY-2000, if the appropriate opportunity arose.

A "window of opportunity" for getting a national nanotechnology initiative underway remains open, said Duncan Moore, associate director for technology at the White House Office of Science and Technology Policy. But Duncan cautioned that such an initiative would require a well-thought-out strategy, with a series of technical and commercial checkpoints. It would also require support within industry, academia, and federal agencies and research institutions.

The workshop did not develop a specific figure for funding the initiative, but some numbers mentioned ranged as high as $150 million.